Organogenesis Holdings Inc. announced that its second Phase 3 randomized controlled trial of ReNu, a cryopreserved amniotic suspension allograft for knee osteoarthritis management, failed to achieve statistical significance for its primary endpoint despite showing numerical improvements over the first Phase 3 study.
Mixed Results Across Phase 3 Program
The 594-patient second Phase 3 trial demonstrated a numerical improvement of -0.51 favoring ReNu over saline control (p=0.0393 one-sided p-value) compared to the target threshold of p=0.023. This fell short of statistical significance, contrasting with the first Phase 3 trial which achieved a statistically significant improvement of -0.72 favoring ReNu (p=0.0177 one-sided p-value).
However, baseline pain reduction at six months showed improvement in the second study, with ReNu achieving -6.9 compared to -6.0 in the first Phase 3 trial, as measured by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. The treatment also demonstrated statistically significant maintenance of function (p<0.0001) and continued to show a favorable safety profile.
Regulatory Strategy Moving Forward
"Given the first Phase 3 trial achieved a statistically significant reduction in pain compared to Saline and the second Phase 3 trial demonstrated a numerical improvement in baseline pain reduction over the first Phase 3, we believe these results support the potential approval of ReNu for pain symptoms associated with knee OA, including those patients classified as most severe," said Patrick Bilbo, Chief Operating Officer of Organogenesis.
The company plans to request a pre-BLA meeting with the FDA by the end of October to discuss the submission pathway, including using combined efficacy analysis from both Phase 3 studies to support a Biologics License Application (BLA) approval.
Comprehensive Clinical Evidence
ReNu has now been studied in three large randomized controlled trials involving more than 1,300 patients combined. The FDA previously granted ReNu Regenerative Medicine Advanced Therapy (RMAT) designation based on its potential to treat an unmet medical need related to knee osteoarthritis.
"The results for ReNu support our continued confidence in the potential of ReNu as an innovative pain management product," said Gary S. Gillheeney, Sr., President, Chief Executive Officer and Chair of the Board for Organogenesis. "We believe ReNu, if approved, will address a significant unmet medical need for the millions of Americans suffering from symptomatic knee OA."
Addressing Significant Medical Need
Knee osteoarthritis is a degenerative joint disease estimated to affect more than 30 million Americans. It ranks among the most common causes of disability and poor quality of life, generally characterized by pain and functionality deficits. End stage management typically involves total knee replacement when all other treatment options are exhausted.
The second Phase 3 trial was a prospective, double-blind, multicenter, saline-controlled, parallel group study of ReNu ASA for treating subjects with mild to severe symptomatic knee osteoarthritis. Patients were randomized to receive a single intra-articular injection of either saline control or ReNu.
ReNu is a cryopreserved amniotic suspension allograft that consists of amniotic fluid cells and micronized amniotic membrane, containing cellular, growth factor, and extracellular matrix components. The therapy received FDA Regenerative Medicine Advanced Therapy designation for knee osteoarthritis in 2021.
